1. Field of the Invention
This invention relates to the treatment of human fingernails and toenails; and more particularly, to topical applications and methods to cure or prevent the spread of nail infections, such as onychomycosis, caused by bacteria, fungi and other pathogens.
2. Description of the Related Art
Onychomycosis is a nail disease of the toes and fingers typically caused by the organisms Candida albicans, Trichophyton mentagrophytes, Trichophyton rubrum, or Epidermpophyton floccusum. The nails become thickened and lusterless, and debris accumulates under the free edge. Nail plates becomes separated and the nails may be destroyed. It is acknowledged that the therapy of onychomycosis is difficult and protracted. Oral therapy with anitmycotics requires months of administration and must be closely monitored for side effects.
Topical compositions have long been used with the objective of treating onychomycosis. Representative compositions used for this purpose are disclosed by U.S. Pat. Nos. 5,346,692; 5,391,367; 5,464,610; 5,487,776; 5,696,105; 5,760,052; 5,840,283; 5,866,105; 5,874,476; 5,916,545; 5,972,317; and 6,022,549. Such prior art topical applications have been largely unsuccessful because the nail is a difficult barrier for anti-fungal compounds to penetrate. To be effective a topical treatment for onychomycosis should exhibit a powerful potency for pathogens. It must also be permeable through the nail barrier, and safe for patient use. There exists a need in the art for a topical application that combines these traits in high degree.
Members of the class of organo-boron compounds have long been known to exhibit biocidal activity. Yet, none of the prior art teachings on treatment of onychomycosis discloses use of compositions containing an organo-boron compound for this purpose, or employs a composition that contains an organo-boron compound as a constituent.
U.S. Pat. No. 3,189,637 to Bengelsdorf et al. describes cycloalkenyl glycol boric acid esters including 2,2′-(alkyldioxy)bis-(alkyl-1,3,2-dioxaborinane) derivatives having utility in a variety of applications, including fungicides.
U.S. Pat. No. 3,877,890 to Maisey et al. describes biocide compositions for controlling and preventing the growth of micro-organisms in jet fuel. The organo-boron compounds of the Maisey et al. patent do not include the dioxaborinane genus of the present invention.
U.S. Pat. No. 4,718,919 to DeLue et al. discloses an anti-icing and biocidal and fungicidal fuel additive including the preferred species of the present invention in combination with an ethylene glycol monoalkylether.
U.S. Pat. No. 4,742,044 to Boden discloses 1,3,2-dioxaborinane derivatives useful in augmenting or enhancing the aroma of perfume compositions, and perfumed articles.
In none of the references describing dioxaborinane compounds is a use for treatment of onychomycosis disclosed or suggested.
The safety and non-toxicity of organo-boron compounds has been questioned.
One reference, “Sax's Dangerous Properties of Industrial Materials”, Tenth Edition, John Wiley & Sons, New York, 2000, P.546, reports that the “Safety Profile” of “Boron Compounds” is “very toxic”, and that “Boron Compounds are therefore considered an industrial poison.”
On the other hand, an article entitled, “Recherces Parmacologiques Sur Les Derives Organiques Du Bore”, Therapie (Paris) 15, 791-802 (1960), discusses the toxicity of the compound 2-(p-tolyl)-(5-methyl, 5-propyl)-1,3,2,-dioxiborinane (termed I.S. 813). When tested for use as a possible sedative, it was found that the toxicity of I.S. 813 was very low. Finally, a fuel additive Biobor® JF containing a combination of 2,2′-(1-methyltrimethylenedioxy)bis-(4-methyl-1,3,2-dioxaborinane) and 2,2′-oxybis(4,4,6-trimethyl-1,3,2-dioxaborinane) with naphtha is sold commercially by Hammonds Fuel Additive Inc., Houston, Tex. The material safety data sheet for this combination identifies as a hazard “Skin Contact: May cause slight to mild irritation. Prolonged or repeated contact may dry the skin and lead to irritation (i.e. dermatitis)”.
There remains a need in the art for a topical application which can be safely applied to nails of fingers and toes, and which exhibits in combination permeability and potency for pathogens required to effectively cure, or prevent the spread of onychomycosis.